This application requests support for a broad analysis of the breast cancer problem. Although the principal emphasis is on the mouse and rat mammary systems, we have recently begun to study mammary cells in vitro. In the rodent system, we will undertake a thorough analysis of the cell populations comprising normal, preneoplastic and neoplastic mammary tissues. Strong emphasis will be given to the development of methods distinguishing between normal, preneoplastic and neoplastic cells, for characterizing transformed cells in vitro, for devising an in vitro infectivity assay for MTV, to distinguish between hormone-dependent and -independent tumors (both rodent and human), and for the prevention of preneoplastic transformation. The role of hormones, mammary tumor viruses, genetically determined susceptibility and resistance factors, immunologic factors, regulatory factors and a variety of non-viral oncogenic factors will be investigated. In addition, one part of our program will be devoted to analysis of oncogenic effects on mice and rats subjected perinatally to different chemical and physical carcinogenic and non-carcinogenic factors and to different environmental factors. Finally, we would use the rodent model in analysis of the factors controlling growth, differentiation and transforming abilities of human breast.